Novel mechanism of rapamycin in GVHD: Increase in interstitial regulatory T cells

J. M. Palmer, B. J. Chen, D. Deoliveira, N. D. Le, N. J. Chao

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Rapamycin (RAPA) is an immunosuppressive drug that prevents and treats graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT). One possible mechanism for its efficacy is induction of tolerance, through increased number or enhanced survival of regulatory T cells. In our experiments, B10.D2 BM and splenocytes were injected into lethally irradiated BALB/cJ recipients. The mice received i.p. injections of either RAPA or vehicle control on days 1-28. There was a significant survival advantage in RAPA-treated mice. Evaluation of the skin biopsies showed a dense cellular infiltrate in RAPA-treated mice. Further characterization of these cells revealed a higher percentage of regulatory T cells characterized by FoxP3-positive cells in high-dose RAPA-treated mice as compared with controls on day 30. This effect appears to be dose dependent. When peripheral blood analysis for FoxP3-positive cells was performed, there was no significant difference observed in the RAPA-treated mice as compared with control mice. These data show a novel mechanism of rapamycin in GVHD, accumulation of regulatory T cells in the GVHD target tissue: the skin.

Original languageEnglish (US)
Pages (from-to)379-384
Number of pages6
JournalBone Marrow Transplantation
Volume45
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Graft-versushost disease
  • Rapamycin
  • Regulatory T cells

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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